The nasal mucosa is the first internal surface to encounter aeroallergens, airborne pathogens, and airborne toxins. Analysis of nasal responses will likely provide insights into normal host defense mechanisms at the mucous membrane level. Allergen challenge results in a direct vascular permeability due to mast cell derived mediators and reflex glandular secretions. An anti-inflammatory agent, nedocromil sodium, had no protective effect on responses caused by allergen. The three divisions of innervation in the nasal mucosa were found to have discrete associations with neuropeptides: The sensory nerves contain GRP (a glandular stimulant), CGRP, SP, and NKA (which act to regulate vasodilation and vascular permeability); the parasympathetic nerves contain VIP (a potent glandular stimulant); and sympathetic nerves contain NPY (a vasoconstrictor). Patients with recurrent sinusitis were found to have a singular defect in nasal secretory responses to cholinergic simulation. Therefore, these patients may be predisposed to recurrent infections by the absence of specific and nonspecific host defense molecules. Uric acid was found to be the major, stable antioxidant in secretions. Uric acid secretion appeared to be glandular in origin. IL-4 caused histamine release in vivo and increased reactivity to histamine releasing factors in vitro. IL-4 induced nasal congestion may be caused by this increased sensitivity. URI's are universally experienced infections causing rhinorrhea. The source of the rhinorrhea during the initial phase of a URI is the vascular bed due to increased vascular permeability. During the resolution phase of a URI, the source of secretions is glandular. The neuropeptide degrading enzyme, NEP, is found in the nasal mucosa and in secretions. We will use the secretion of NEP to monitor its role in airway reactivity. Nasal urea allows a close estimate of the volume of the epithelial lining fluid, and calculation of the actual concentration of molecules in secretions. These nasal urea measurements will greatly enhance the analysis of nasal secretions.